Senile dementia of Alzheimer's type (SDAT) is characterized by progressive deficits of multiple cognitive functions in elderly more than 65 years of age. The APOE-epsilon 4 allele has been shown to be a risk factor for SDAT. To investigate the genetic interactions between SDAT and the APOE/APOC1/APOC2 gene cluster located at 19q13.2, we genotyped these genes in patients with SDAT and nondemented controls. Although allelic associations were found between the APOC1 locus and SDAT (p = 0.0022) as well as between the APOE locus and SDAT (p < 0.0001), no associations were detected between the APOC2 locus and SDAT. And the association between the APOE and APOC1 locus in SDAT was statistically more significant than that in controls (p < 0.001). Estimation of the haplotype frequencies indicated that the association between the APOE/APOC1 haplotype and SDAT was more significant than linkage disequilibrium between the APOE and APOC1 locus (p < 0.01). These results suggest that genetic interaction between the APOE and APOC1 gene could modify a risk factor of APOE-epsilon 4 for SDAT. The APOE/APOC1 locus was estimated to be responsible for 54.8% of SDAT in the Japanese population.